Ciencia, vino y salud

A large number of prospective studies have observed an inverse relationship between a moderate intake of alcohol and coronary heart disease morbidity and mortality. Concerning death from all-causes, results are not unanimous. Alcohol intake was associated with a protection of all-cause mortality in England and USA physicians and the large study of the American Cancer Society. None of these studies separated the effects of different alcoholic beverages. In our prospective studies in France on 35 000 middle-aged men, we observed that only wine at moderate intake, was associated with a protective effect on all-cause mortality. The reason was that in addition to the known effect on cardiovascular diseases, a very moderate intake of wine, protected also from cancer and other causes as confirmed by Gronbaek in Denmark. Our recent results also indicate that the protective effect of a moderate intake of wine on all-cause mortality is observed at all levels of blood pressure and serum cholesterol.

Mediterranean diet, but not red wine, is associated with beneficial changes in primary haemostasis.

OBJECTIVE: (1) To compare the effect of an alcohol-free Mediterranean-type diet (MD) and a high-fat diet (HFD) on variables of primary haemostasis (bleeding time, plasma von Willebrand factor and platelet aggregation/secretion). (2) To test whether red wine supplementation modified these variables, independently of the diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each consisting of 21 healthy male university students (22+/-3.4 y), received either MD or HFD during 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline (T0) and T30, T60 and T90-day samples were drawn. Bleeding time was measured before (day 30) and after (day 60) wine supplementation. No drop out from the study was experienced. SETTING: University campus and outpatient nutrition clinic. RESULTS: All baseline (day 0) variables did not differ significantly between study groups. On day 30, individuals on MD had significantly higher levels of plasma beta-carotene, folate, ascorbate, and eicosapentaenoic acid in plasma lipid fractions, than those on HFD. Total plasma cholesterol, HDL and LDL did not change significantly in either study group at any time point. After 30 days on each diet, individuals on MD had longer bleeding time (BT) than those on HFD (7.6+/-2.8 vs 5.8+/-1.7 min; P=0.017). BT did not change significantly after I month of wine supplementation (7.1+/-2.0 vs 5.5+/-2.0 min, respectively). Plasma von Willebrand factor (vWF : Ag) on day 0 was 89+/-40 and 111+/-70% in MD and HFD groups, respectively (P=0.21). These values did not change significantly at 30, 60 or 90 days. MD intake was associated with an increase in platelet serotonin secretion (P=0.02) and a marginal increase in platelet aggregation after stimulation with epinephrine (P=0.07). Wine intake resulted in a marginal decrease in platelet (14)C-5-HT secretion with 4 micro M ADP (P=0.07). However, both platelet aggregation and secretion were consistently increased when using collagen as agonist (1 and 2 micro g/ml, P=0.01). CONCLUSION: The longer BT in individuals on MD, obtained independently of red wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of view of cardiovascular (CV) risk. This effect is not explained by changes in the measured haemostatic determinants of BT (plasma vWF, ex vivo platelet function), and might be attributed to other as yet unknown vascular factors. Moderate consumption of red wine results in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen. This observation contradicts previous reports, although further studies are required to elucidate the influence of this finding on CV risk.

Ingesta de nutrientes en adultos mayores de la comuna de Providencia, Santiago de Chile / Nutrients intake in elderly people living in Providence, Santiago de Chile

BACKGROUND: The information available on food intake in the elderly in Chile is restricted to individuals of low socioeconomic groups, but there is no data available on food intake in elderly of higher income groups. AIM: To assess food intake in a group of elderly people from Providencia County in Santiago, a middle income community. SUBJECTS AND METHODS: Forty one subjects (20 male), aged 60 to 73 years, were studied. Trained volunteers applied a 3 days food registry, to determine food intake. Intake was assessed using 1985 FAO/OMS/UNU recommendations for energy intake and USA Food and Nutrition Board recommendations for micronutrient intake. RESULTS: The studied subjects had an adequate macronutrient intake, when compared with current recommendations. There was a relatively low intake of calories from fat (24.6 per cent in males and 26.1 per cent in females). Also, vitamin and mineral intake was adequate with the exception of calcium (64.5 per cent and 57.9 per cent of recommendation in males and in females respectively), zinc and folic acid (74.2 per cent and 62.4 per cent in males and females respectively). The intake of legumes and cereals was relatively low. CONCLUSIONS: Food intake in this group of individuals was substantially higher than that reported previously for poor elderly Chileans and similar to that of industrialized countries. Food intake of the elderly is probably related to socioeconomic level.

Inflammation, not hyperhomocysteinemia, is related to oxidative stress and hemostatic and endothelial dysfunction in uremia.

BACKGROUND: Several cardiovascular risk factors are present in patients with chronic renal failure (CRF), among which are systemic inflammation and hyperhomocysteinemia. Increased oxidative stress, endothelial activation/dysfunction, and coagulation activation are considered integral components of the inflammatory response, but have also been proposed as mediators of plasma homocysteine (tHcy)-induced cell damage. Using correlation analysis, we assessed the relative contributions of inflammation and hyperhomocysteinemia in the abnormal oxidative stress, endothelial activation/dysfunction, and hemostasis activation in patients with CRF. METHODS: The relationships of inflammatory proteins and tHcy with plasma markers of these processes were studied in 64 patients with CRF (serum creatinine 526 +/- 319 micromol/L) on conservative treatment, comparing the results with healthy controls (N = 15 to 40, depending on the measured variable) of similar sex and age. RESULTS: Patients had significant increases in inflammatory cytokines (TNF-alpha and IL-8) and acute-phase proteins (C-reactive protein, fibrinogen and alpha1-antitrypsin). tHcy was increased in 87.5% of patients (mean = 27.1 micromol/L, range 6.5 to 118). Patients had significant increases in (1) indices of oxidative stress: TBARS (thiobarbituric acid-reactive species), a marker of lipid peroxidation and AOPP (advanced oxidation protein products), a marker of protein oxidation; (2) endothelial cell markers such as von Willebrand factor (vWF:Ag), soluble ICAM-1 and soluble thrombomodulin (sTM); (3) markers of intravascular thrombin generation: thrombin-antithrombin complexes (TAT) and prothrombin fragment F(1+2) (PF(1+2)); and (4) indices of activation of fibrinolysis: plasmin-antiplasmin complexes (PAP), fibrin degradation products (FnDP) and fibrinogen degradation products (FgDP). tHcy was significantly correlated with plasma creatinine (r = 0.29, P < 0.018) and with serum folate (r = -0.38, P < 0.002). However, no significant correlations were observed between tHcy and TBARS, AOPP, vWF:Ag, sICAM-1, sTM, TAT, F(1+2), sTF, PAP, FnDP, and FgDP. Conversely, acute-phase proteins showed significant, positive correlations with most markers of oxidative stress, endothelial dysfunction and hemostatic activation. CONCLUSIONS: Systemic inflammation, which is closely associated with augmented oxidative stress, endothelial cell dysfunction and hemostatic activation, emerges as a major cardiovascular risk factor in CRF. tHcy is unrelated to these events. Thus, alternative mechanisms through which hyperhomocysteinemia could predispose to vascular lesion and thrombotic events in CRF needs to be investigated.

Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors.

OBJECTIVES: To compare the effect of alcohol-free Mediterranean-type diet (MD) and high-fat diet (HFD) on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF). Also, to test if red wine supplementation modifies HCVRF, independent of diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each of 21 healthy male university students (22+/-3.4 y), received either MD or HFD for 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline and T30, T60 and T90-day samples were drawn. No drop out from the study was observed. SETTING: University campus and outpatient nutrition clinic. RESULTS: Volunteers on HFD at T30 had increases in pro-coagulants fibrinogen (22%), factor VIIc (9%), and factor VIIIc (4%), and decreases in natural anticoagulants antithrombin III (3%), protein C (11%) and protein S (6%) and of 20% in plasminogen activator inhibitor-1. At the same time, individuals on MD had increases in fibrinogen (4%), antithrombin III (5%), protein C (3%), protein S (2.7%), and decreases in factor VIIIc (9%), and plasminogen activator inhibitor-1 (21%). After adjusting by baseline values, MD was associated with lower plasma fibrinogen (P=0.03), factor VIIc (P=0.034) and factor VIIIc (P=0.0057) and with higher levels of protein S (P=0.013). Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen (P=0.001) and factor VIIc (P=0.05), and increased tissue plasminogen activator antigen (P=0.01) and plasminogen activator inhibitor-1 antigen (P=0.0003). Wine consumption was also associated with significantly (P=0.01) divergent effects on antithrombin III: it decreased by 10% in individuals on HFD but increased slightly in those on MD. No effects of diet or wine were detected in plasma protein C and C-reactive protein. CONCLUSION: MD and moderate consumption of red wine have complementary, mostly beneficial effects on HCVRF.

[Differences in plasma antioxidants according to socioeconomic level in Chilean women]. / Diferencias en antioxidantes plasmáticos según nivel socioeconómico en mujeres chilenas.

BACKGROUND: Free radical-mediated oxidative damage is a known initial event in atherogenesis. Cardiovascular disease is frequent in the Chilean population showing differences in the prevalence of risk factors of the disease according to socioeconomic level (SEL). AIM: To determine levels of antioxidants and lipid peroxides in Chilean women from different SEL. PATIENTS AND METHODS: Blood samples were taken from 81 women for measurements of plasma ascorbic acid, beta-carotene, alpha-tocopherol, licopene, ubiquinol, glutathione, total plasma antioxidant capacity, and lipid peroxides (TBARS). RESULTS: Individuals in the lower SEL showed reduced levels of plasma beta-carotene, ascorbic acid, alpha-tocopherol, and ubiquinol compared to women in the higher SEL. There were no differences between groups in the plasma levels of glutathione, total antioxidant capacity, or TBARS. CONCLUSIONS: The results could be explained in part by the higher consumption of fruits and vegetables in women from the upper SEL.

Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids.

Hyperhomocysteinemia in association with vitamin B(12) deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B(12) normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 microg) in 18 individuals, serum vitamin B(12) increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 micromol/L (p<0. 0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B(12) and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.

The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease.

One of the theories involved in the etiology of Alzheimer's disease (AD) is the oxidative stress hypothesis. The amyloid beta-peptide (A beta), a hallmark in the pathogenesis of AD and the main component of senile plaques, generates free radicals in a metal-catalyzed reaction inducing neuronal cell death by a reactive oxygen species mediated process which damage neuronal membrane lipids, proteins and nucleic acids. Therefore, the interest in the protective role of different antioxidants in AD such as vitamin E, melatonin and estrogens is growing up. In this review we summarize data that support the involvement of oxidative stress as an active factor in A beta-mediated neuropathology, by triggering or facilitating neurodegeneration, through a wide range of molecular events that disturb neuronal cell homeostasis.

Plant polyphenol antioxidants and oxidative stress.

In recent years there has been a remarkable increment in scientific articles dealing with oxidative stress. Several reasons justify this trend: knowledge about reactive oxygen and nitrogen species metabolism; definition of markers for oxidative damage; evidence linking chronic diseases and oxidative stress; identification of flavonoids and other dietary polyphenol antioxidants present in plant foods as bioactive molecules; and data supporting the idea that health benefits associated with fruits, vegetables and red wine in the diet are probably linked to the polyphenol antioxidants they contain. In this review we examine some of the evidence linking chronic diseases and oxidative stress, the distribution and basic structure of plant polyphenol antioxidants, some biological effects of polyphenols, and data related to their bioavailability and the metabolic changes they undergo in the intestinal lumen and after absorption into the organism. Finally, we consider some of the challenges that research in this area currently faces, with particular emphasis on the contributions made at the International Symposium "Biology and Pathology of Free Radicals: Plant and Wine Polyphenol Antioxidants" held July 29-30, 1999, at the Catholic University, Santiago, Chile and collected in this special issue of Biological Research.

A comparison of methods employed to evaluate antioxidant capabilities.

Three different methodologies frequently employed to evaluate the indexes that report the antioxidant capabilities of pure compounds and/or complex mixtures of antioxidants are applied to a series of mono- and polyphenols, as well as to two wine (red and white) samples. These methodologies are based on the bleaching of a stable radical, the effect of the additive upon luminol chemiluminescence induced by peroxyl radicals, and the effect of the additive upon the bleaching of the fluorescence from a dye molecule. Widely different responses are obtained from the different methodologies. These differences are interpreted in terms of the different factors (stoichiometric factors and/or reactivities) that determines the indexes evaluated by these different methodologies.

Endothelial cell oxidative stress and signal transduction.

Endothelial dysfunction (ED) is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS) have been implicated as important mechanisms that contribute to ED, and ROS's may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1), tyrosine kinases (Src and Syk) and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC), we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy) and oxidized LDL (oxLDL) enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process.

Endothelial cell oxidative stress and signal transduction

Endothelial dysfunction (ED) is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS) have been implicated as important mechanisms that contribute to ED, and ROS's may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1), tyrosine kinases (Src and Syk) and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC), we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy) and oxidized LDL (oxLDL) enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process.

A comparison of methods employed to evaluate antioxidant capabilities

Three different methodologies frequently employed to evaluate the indexes that report the antioxidant capabilities of pure compounds and/or complex mixtures of antioxidants are applied to a series of mono- and polyphenols, as well as to two wine (red and white) samples. These methodologies are based on the bleaching of a stable radical, the effect of the additive upon luminol chemiluminescence induced by peroxyl radicals, and the effect of the additive upon the bleaching of the fluorescence from a dye molecule. Widely different responses are obtained from the different methodologies. These differences are interpreted in terms of the different factors (stoichiometric factors and/or reactivities) that determines the indexes evaluated by these different methodologies.

Plant polyphenol antioxidants and oxidative stress

In recent years there has been a remarkable increment in scientific articles dealing with oxidative stress. Several reasons justify this trend: knowledge about reactive oxygen and nitrogen species metabolism; definition of markers for oxidative damage; evidence linking chronic diseases and oxidative stress; identification of flavonoids and other dietary polyphenol antioxidants present in plant foods as bioactive molecules; and data supporting the idea that health benefits associated with fruits, vegetables and red wine in the diet are probably linked to the polyphenol antioxidants they contain. In this review we examine some of the evidence linking chronic diseases and oxidative stress, the distribution and basic structure of plant polyphenol antioxidants, some biological effects of polyphenols, and data related to their bioavailability and the metabolic changes they undergo in the intestinal lumen and after absorption into the organism. Finally, we consider some of the challenges that research in this area currently faces, with particular emphasis on the contributions made at the International Symposium [quot ]Biology and Pathology of Free Radicals: Plant and Wine Polyphenol Antioxidants[quot ] held July 29-30, 1999, at the Catholic University, Santiago, Chile and collected in this special issue of Biological Research.

Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans.

An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.

Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells.

The signaling mechanism through which deficitary mitochondrial function would activate nuclear genes required for mitochondrial biogenesis, has not been established. To explore the hypothesis that reactive oxygen species (ROS), a mitochondrial product, constitute part of the mitochondria-nuclei signaling pathway, we obtained HeLa cells depleted of mitochondrial DNA (rho0 cells) through exposure to ethidium bromide. We found evidences of oxidative stress in rho0 cells, employing a fluorescent probe and measuring NF-kappaB activation. Nuclear Respiratory Factor-1 (NRF-1) and Mitochondrial Transcription Factor A (Tfam) mRNA were measured by RT-PCR. For both transcription factors, rho0 cells revealed significantly higher levels of mRNA. These results support several hypothesis: that endogenous ROS enhance the expression of nuclear mitochondrial biogenesis genes NRF-1 and Tfam; that DNA deprived mitochondria lead to cellular oxidative stress, probably because of incomplete biogenesis of the mitochondrial electron transport chain, and consequently, that ROS are part of a mitochondria-nuclei regulatory signaling pathway.

[Wine and health. Epidemiological studies and possible mechanisms of the protective effects]. / Vino y salud. Estudios epidemiológicos y posibles mecanismos de los efectos protectores.

Epidemiological studies show that moderate alcohol consumption, particularly wine, is associated to a decreased risk of ischemic heart disease death. A series of in vitro observations also support this association. Low density lipoproteins (LDL) oxidation apparently plays a key pathogenic role. Wine contains compounds with antioxidant capacity that could account for its postulated stabilizing effect on LDL. Furthermore, in human volunteers wine increases plasma total antioxidant capacity. Other additional effects also contribute to decrease the risk of ischemic heart disease: increased HDL cholesterol, and decreased blood coagulation. In another series of observations, moderate alcohol consumption has been associated with decreased physical and mental deterioration in elderly people. However, it is still under analysis if exaggerated alcohol consumption does increase the incidence of some cancers. On the whole, the presently available evidences clearly indicate that the positive effects associated to moderate wine or alcohol consumption, predominate over the negative effects. In fact, it seems reasonable to reassure moderate alcohol consumers that their cardiovascular death risk is lower; yet there are not enough studies to recommend moderate drinking to non-drinkers.